Abstract #1999: Circulating endothelial cells (CECs) and progenitors (CEPs) for prediction of response in patients with breast cancer who receive chemotherapy and anti-angiogenic drugs: Different predictive potentials according to drug dose and schedule.

Abstract

The addition of anti-angiogenic drugs to chemotherapy has led to improved survival in randomized trials involving colorectal, lung and breast cancer patients. However, this survival advantage was short, and was probably due to a larger benefit in a selected (but yet unrecognized) patient population rather than in the entire treated population. We investigated the kinetics and the predictive potential of CECs and CEPs in 4 phase II studies in which patients with advanced or locally advanced breast cancer received metronomic chemotherapy alone, metronomic chemotherapy plus the anti-VEGF antibody bevacizumab or regular-dose chemotherapy plus bevacizumab. CECs and CEPs were measured with a novel flow cytometry procedure including nuclear acid staining (Syto16 and 7AAD) able to investigate CEC/CEP viability and to discriminate between nucleated CECs/CEPs, CEC-derived fragments and platelets (Mancuso et al, Clin Cancer Res, in press). Compared with healthy controls, CECs (CD45-, CD31+, CD146+) and CEPs (either CD45-, CD133+ or CD45-, CD34+, VEGFR2+) were increased in patients with cancer, and in particular in patients with advanced breast cancer, where CEC count was found to be one log higher compared to controls. In patients receiving oral metronomic chemotherapy alone (either cyclophosphamide (CTX) plus methotrexate, in one study enrolling 104 patients, or vinorelbine alone, in another study enrolling 35 patients), therapy was associated with a decrease in viable CECs, and an increase in apoptotic CECs. In patients receiving CTX plus methotrexate, an increase in apoptotic CECs after two months of therapy was associated with improved survival (p=0.005). In another study enrolling patients with advanced breast cancer receiving metronomic capecitabine plus CTX plus bevacizumab (n=46), higher baseline CEC counts correlated with an improved response (p=0.02), clinical benefit (p=0.01) and progression-free survival (p=0.04). In a fourth study were 36 locally advanced patients received regular-dose chemotherapy (capecitabine plus vinorelbine), plus endocrine therapy (letrozole) plus bevacizumab before surgery, baseline CEP count was positively associated with a clinical response (p=0.02). Taken together, our studies indicate that assessment of CECs might be an estimation tool for prediction of response in patients with advanced breast cancer receiving metronomic chemotherapy alone or in association with bevacizumab. On the other hand, CEPs might be more promising for predicting response in patients receiving regular-dose chemotherapy plus anti-angiogenic drugs.

Abstract #1999: Circulating endothelial cells (CECs) and progenitors (CEPs) for prediction of response in patients with breast cancer who receive chemotherapy and anti-angiogenic drugs: Different predictive potentials according to drug dose and schedule.

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Abstract #1999: Circulating endothelial cells (CECs) and progenitors (CEPs) for prediction of response in patients with breast cancer who receive chemotherapy and anti-angiogenic drugs: Different predictive potentials according to drug dose and schedule.